Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization

Ecological phytochemistry of Cerrado (Brazilian savanna) plants

The Cerrado (the Brazilian savanna) is one of the vegetation formations of great biodiversity in Brazil and it has experienced strong deforestation and fragmentation. The Cerrado must contain at least 12,000 higher plant species.We discuss the ecological relevance of phytochemical studies carried out on plants from the Cerrado, including examples of phytotoxicity, antifungal, insecticidal and antibacterial activities. The results have been classified according to activity and plant family. The most active compounds have been highlighted and other activities are discussed. A large number of complex biochemical interactions occur in this system. However, only a small fraction of the species has been studied from the phytochemical viewpoint to identify the metabolites responsible for these interactions

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Regulation of gene expression in entomopathogenic fungi in three different environmental conditions: A review

The entomopathogenic fungi are subject to regulation system known as signal transduction that regulates the expression of the different genes required for each life stage, first comprising cuticle adhesion and degradation, later the survival in the hemolymph, and finally the fungal growth in soils. There are two signal-transduction mechanisms identified in the entomopathogenic fungi: mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) dependent to cAMP pathway together with regulatory G protein signaling; both pathways participate in activation of genes linked to virulence for certain environments and hosts such as adhesion, formation of appressorium and penetration pegs, synthesis of cuticle-degrading enzymes, survival in hemolymph to evade insect immune responses, and osmolarity changes. Also, activating well-defined gene sets involved in entomopathogenic fungal survival on non-insect substrates as saprophytes or root colonizer utilized the nutrients present in root exudates, facilitating entomopathogenic fungi to act as endophytes.Keywords: Entomopathogenic fungi, signal transduction, mitogen-activated protein kinases (MAPK), protein kinase A (PKA)African Journal of Biotechnology Vol. 12(10), pp. 989-995, 6 March, 201

Revaluation of Local Waste through an Ecotechnologies Strategic Plan: A Case Study with Digesters

In Mexico, the accelerated and unplanned growth of population causes the increment in informal facilities, complicating access to essential services such as adequate sanitation and organic waste management, where the most affected are usually the vulnerable population. The Mexican government has implemented programs and support to encourage the use of ecotechnologies and thus provide alternatives to improve their living conditions by taking advantage of local resources and waste. However, these programs and supports lack planning, creating little interest from users. This research proposes an acceptance strategy for the integration of ecotechnologies that adapt to the lifestyle of populations that need an alternative for their method of sanitation and organic waste management. The strategy is mainly based on a course of action that operates with four main lines of intervention. It was executed as a practical exercise with biodigesters, in the Mexican community of La Trinidad, in the municipality of Tequisquiapan, Quer&eacute;taro. With the help of the strategy, important factors for the end-user were identified that must be considered when integrating one ecotechnology into the population. In general terms, the strategy showed an improvement in sanitation and organic waste management and a greater acceptance of biodigesters as an alternative of use

Revaluation of Local Waste through an Ecotechnologies Strategic Plan: A Case Study with Digesters

In Mexico, the accelerated and unplanned growth of population causes the increment in informal facilities, complicating access to essential services such as adequate sanitation and organic waste management, where the most affected are usually the vulnerable population. The Mexican government has implemented programs and support to encourage the use of ecotechnologies and thus provide alternatives to improve their living conditions by taking advantage of local resources and waste. However, these programs and supports lack planning, creating little interest from users. This research proposes an acceptance strategy for the integration of ecotechnologies that adapt to the lifestyle of populations that need an alternative for their method of sanitation and organic waste management. The strategy is mainly based on a course of action that operates with four main lines of intervention. It was executed as a practical exercise with biodigesters, in the Mexican community of La Trinidad, in the municipality of Tequisquiapan, Querétaro. With the help of the strategy, important factors for the end-user were identified that must be considered when integrating one ecotechnology into the population. In general terms, the strategy showed an improvement in sanitation and organic waste management and a greater acceptance of biodigesters as an alternative of use